Design, docking, molecular dynamics, synthesis and antimicrobial studies on quinoline derivatives and some isosteres

Abstract

The computer added design, synthesis, antibacterial and antifungal activities of a series of quinoline derivatives and some isosteres are reported. In silico studies using autodock software have shown that all compounds exhibited excellent interaction within active site of peptide deformylase (PDF) protein (PDB ID: 1G2A) and formed hydrogen bonds with Gly43, Arg97, Glu133, Ile44, Gly45, Cys90, Gly42, His132, Ile93 amino acid residues of PDF protein. Antibacterial screening showed a great extent of inhibitory activity of compound 2 (MIC, up to 3.12 µg/mL) and compound 6 (MIC, up to1.56 µg/mL) against different human pathogenic bacteria, viz. B. cerus, S. aureus, E. coli and P. aeruginosa vis-à-vis reference drugs like chloramphenicol, sulfamethoxazole and ciprofloxacin. Further, combinatorial antibacterial screening with reference drugs using different methods revealed that the combined MICs of compounds were lowered by 1/2 to 1/34 of their original MICs. Antifungal screening indicated that compounds were also potentially active against several species of pathogenic fungal strains, viz. A. flavus, A. niger, F. oxysporum and C. albicans. Compound 1 showed good antifungal activity against A. flavus and F. oxysporium with inhibitory index 92% and 91%, respectively. Additionally, the molecular dynamics (MD) simulation, performed on compounds 2 and 6, showed that both the compounds formed very stable complexes with PDF protein. The study suggested that the compounds 1, 2 and 6 could be developed as potential ingredients of possible effective drug regimens.